4c0d

From Proteopedia

Revision as of 11:56, 20 November 2013

Template:STRUCTURE 4c0d

Structure of the NOT module (CNOT1-CNOT2-CNOT3) of the human CCR4-NOT complex

Template:ABSTRACT PUBMED 24121232

Disease

[CNOT3_HUMAN] Precursor T-cell acute lymphoblastic leukemia.

Function

[CNOT1_HUMAN] Belongs to the CCR4-NOT complex that functions as general transcription regulation complex. Acts as a transcriptional repressor. Represses the ligand-dependent transcriptional activation by nuclear receptors.^{[1] [2]} [CNOT3_HUMAN] Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. May be involved in metabolic regulation; may be involved in recruitment of the CCR4-NOT complex to deadenylation target mRNAs involved in energy metabolism. Involved in mitotic progression and regulation of the spindle assembly checkpoint by regulating the stability of MAD1L1 mRNA. Can repress transcription and may link the CCR4-NOT complex to transcriptional regulation; the repressive function may involve histone deacetylases. Involved in the maintenance of emryonic stem (ES) cell identity.^{[3] [4] [5]} [CNOT2_HUMAN] Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Required for the CCR4-NOT complex structural integrity. Can repress transcription and may link the CCR4-NOT complex to transcriptional regulation; the repressive function may specificly involve the N-Cor repressor complex containing HDAC3, NCOR1 and NCOR2. Involved in the maintenance of emryonic stem (ES) cell identity.^{[6] [7] [8] [9]}

About this Structure

4c0d is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA.

Reference

• Boland A, Chen Y, Raisch T, Jonas S, Kuzuoglu-Ozturk D, Wohlbold L, Weichenrieder O, Izaurralde E. Structure and assembly of the NOT module of the human CCR4-NOT complex. Nat Struct Mol Biol. 2013 Oct 13. doi: 10.1038/nsmb.2681. PMID:24121232 doi:http://dx.doi.org/10.1038/nsmb.2681

1. ↑ Albert TK, Lemaire M, van Berkum NL, Gentz R, Collart MA, Timmers HT. Isolation and characterization of human orthologs of yeast CCR4-NOT complex subunits. Nucleic Acids Res. 2000 Feb 1;28(3):809-17. PMID:10637334
2. ↑ Winkler GS, Mulder KW, Bardwell VJ, Kalkhoven E, Timmers HT. Human Ccr4-Not complex is a ligand-dependent repressor of nuclear receptor-mediated transcription. EMBO J. 2006 Jul 12;25(13):3089-99. Epub 2006 Jun 15. PMID:16778766 doi:7601194
3. ↑ Zwartjes CG, Jayne S, van den Berg DL, Timmers HT. Repression of promoter activity by CNOT2, a subunit of the transcription regulatory Ccr4-not complex. J Biol Chem. 2004 Mar 19;279(12):10848-54. Epub 2004 Jan 5. PMID:14707134 doi:http://dx.doi.org/10.1074/jbc.M311747200
4. ↑ Takahashi A, Kikuguchi C, Morita M, Shimodaira T, Tokai-Nishizumi N, Yokoyama K, Ohsugi M, Suzuki T, Yamamoto T. Involvement of CNOT3 in mitotic progression through inhibition of MAD1 expression. Biochem Biophys Res Commun. 2012 Mar 9;419(2):268-73. doi:, 10.1016/j.bbrc.2012.02.007. Epub 2012 Feb 10. PMID:22342980 doi:http://dx.doi.org/10.1016/j.bbrc.2012.02.007
5. ↑ Zheng X, Dumitru R, Lackford BL, Freudenberg JM, Singh AP, Archer TK, Jothi R, Hu G. Cnot1, Cnot2, and Cnot3 maintain mouse and human ESC identity and inhibit extraembryonic differentiation. Stem Cells. 2012 May;30(5):910-22. doi: 10.1002/stem.1070. PMID:22367759 doi:http://dx.doi.org/10.1002/stem.1070
6. ↑ Zwartjes CG, Jayne S, van den Berg DL, Timmers HT. Repression of promoter activity by CNOT2, a subunit of the transcription regulatory Ccr4-not complex. J Biol Chem. 2004 Mar 19;279(12):10848-54. Epub 2004 Jan 5. PMID:14707134 doi:http://dx.doi.org/10.1074/jbc.M311747200
7. ↑ Jayne S, Zwartjes CG, van Schaik FM, Timmers HT. Involvement of the SMRT/NCoR-HDAC3 complex in transcriptional repression by the CNOT2 subunit of the human Ccr4-Not complex. Biochem J. 2006 Sep 15;398(3):461-7. PMID:16712523 doi:http://dx.doi.org/10.1042/BJ20060406
8. ↑ Ito K, Inoue T, Yokoyama K, Morita M, Suzuki T, Yamamoto T. CNOT2 depletion disrupts and inhibits the CCR4-NOT deadenylase complex and induces apoptotic cell death. Genes Cells. 2011 Apr;16(4):368-79. doi: 10.1111/j.1365-2443.2011.01492.x. Epub, 2011 Feb 8. PMID:21299754 doi:http://dx.doi.org/10.1111/j.1365-2443.2011.01492.x
9. ↑ Zheng X, Dumitru R, Lackford BL, Freudenberg JM, Singh AP, Archer TK, Jothi R, Hu G. Cnot1, Cnot2, and Cnot3 maintain mouse and human ESC identity and inhibit extraembryonic differentiation. Stem Cells. 2012 May;30(5):910-22. doi: 10.1002/stem.1070. PMID:22367759 doi:http://dx.doi.org/10.1002/stem.1070